Variant 3-75937590-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP6

The NM_001378191.1(ROBO2):c.97G>T(p.Gly33Ter) variant causes a stop gained change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ROBO2
NM_001378191.1 stop_gained

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: 5.00

Variant links:

Genes affected

ROBO2 (HGNC:10250): (roundabout guidance receptor 2) The protein encoded by this gene belongs to the ROBO family, part of the immunoglobulin superfamily of proteins that are highly conserved from fly to human. The encoded protein is a transmembrane receptor for the slit homolog 2 protein and functions in axon guidance and cell migration. Mutations in this gene are associated with vesicoureteral reflux, characterized by the backward flow of urine from the bladder into the ureters or the kidney. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2014]

ROBO2 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP6

Variant 3-75937590-G-T is Benign according to our data. Variant chr3-75937590-G-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 224347.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}. Variant chr3-75937590-G-T is described in Lovd as [Benign].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons
ROBO2	NM_001378191.1 linkuse as main transcript	c.97G>T	p.Gly33Ter	stop_gained	2/30
ROBO2	NM_001378190.1 linkuse as main transcript	c.97G>T	p.Gly33Ter	stop_gained	2/29
ROBO2	NM_001378195.1 linkuse as main transcript	c.97G>T	p.Gly33Ter	stop_gained	2/29

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL
ROBO2	ENST00000696630.1 linkuse as main transcript	c.97G>T	p.Gly33Ter	stop_gained	2/30
ROBO2	ENST00000696629.1 linkuse as main transcript	c.97G>T	p.Gly33Ter	stop_gained	2/29
ROBO2	ENST00000471893.2 linkuse as main transcript	c.97G>T	p.Gly33Ter	stop_gained	2/29	4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0195

AC:

3534

AN:

181206

Hom.:

AF XY:

0.0197

AC XY:

1962

AN XY:

99442

show subpopulations

Gnomad AFR exome

AF:

0.00163

Gnomad AMR exome

AF:

0.0215

Gnomad ASJ exome

AF:

0.0327

Gnomad EAS exome

AF:

0.0000573

Gnomad SAS exome

AF:

0.0124

Gnomad FIN exome

AF:

0.0168

Gnomad NFE exome

AF:

0.0275

Gnomad OTH exome

AF:

0.0226

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

1403380

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

695790

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.124

Hom.:

ExAC

AF:

0.0736

AC:

8607

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Vesicoureteral reflux 2

Uncertain:1

Uncertain significance, criteria provided, single submitter

research

Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine

- -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Aug 01, 2023

ROBO2: BS1 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Pathogenic

0.56

BayesDel_noAF

Pathogenic

0.57

CADD

Pathogenic

DANN

Uncertain

0.99

Eigen

Pathogenic

0.88

Eigen_PC

Pathogenic

0.69

FATHMM_MKL

Uncertain

0.82

Vest4

0.50

GERP RS

4.5

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over